Investigating problematic severe asthma in children : a translational approach

Children with problematic severe asthma (PA) have persistent symptoms and/or severe exacerbations despite treatment with high doses of currently available asthma medications. The term PA includes children who are difficult to treat due to unidentified exacerbating factors (e.g. allergens or environmental hazards, comorbidities, psychological and social issues, and/or poor adherence) and those lacking identifiable aggravating factors but, nonetheless, do not respond well to asthma therapy. Children with PA are a heterogeneous group of patients with varying clinical presentations, pulmonary function and patterns of inflammation. This thesis is based on the results of a Swedish nationwide cross-sectional study in which school aged children with PA (n=57) were compared to age matched peers with persistent, but controlled asthma (CA), (n=39). The major objectives were to identify distinguishing features of children suffering from PA, to differentiate between children who were difficult to treat and those who were severely resistant to therapy and to investigate novel and potentially clinical relevant biomarkers of PA. PA was defined by insufficient asthma control despite high doses of inhaled corticosteroids. The protocol included a detailed characterization of: history and clinical presentation; pulmonary function; bronchial hyperresponsiveness; inflammatory biomarkers in blood (including white blood cells, interleukin-5 and chitinases (chitotriosidase and the chitinase-like protein YKL-40)), urine (EPX) and exhaled air (FeNO); allergy (IgE antibodies, component resolved allergy diagnostics, basophil allergen threshold sensitivity (CD-sens)); morphology (computerized tomography of sinuses and lungs (in the PA group only)). The major distinguishing features of children with PA involve familial background (heredity, socioeconomic status), clinical presentation (comorbidities and triggering factors) and pathophysiological differences including degree of airway obstruction, bronchial hyperresponsiveness and inflammatory profile (IL-5, number of eosinophilic and neutrophilic cells in blood). Sixty percent of children with PA had therapy-resistant asthma, with the remainder being difficult to treat due to identified aggravating factors. Individual IgE-responses were similar between children with PA and CA. Children with PA were more often multi-sensitized to > 3 single lipocalin (nMus m 1, rEqu c 1, Fel d 4, rCan f 1, 2), kallikrein (rCan f 5) and secretoglobin (rFel d 1) allergens compared to children with CA. Cat-allergic children with PA had higher allergen sensitivity, as measured by CDsens, compared to cat-allergic peers with CA. Furthermore, CD-sens correlated with clinical markers of asthmatic disease, including asthma control and biomarkers of eosinophilic inflammation. YKL-40 levels and chitotriosidase activity were increased in the serum of children with PA, and YKL-40 specifically correlated with airway remodelling (as assessed by computerized tomography) and blood neutrophils in children severely resistant to asthma therapy. By employing a comprehensive and standardized clinical assessment we have discerned specific features of children with PA and identified children who are severely resistant to therapy. We have applied two novel methods of allergy diagnostics (Component resolved diagnostics and CD-sens) and found that these two methods provide relevant information when investigating children with PA. Finally, our findings confirm that YKL-40 is a potential biomarker of asthma severity and airway remodeling. A translational research approach is necessary when investigating associations between disease mechanisms and clinical presentation in complex diseases

Congenital ectopia lentis : diagnosis and treatment

Congenital ectopia lentis (EL) is an ocular condition, which typically causes a high grade of refractive errors, mainly myopia and astigmatism. These might be difficult to compensate for, especially in children, who might develop ametropic amblyopia. Surgery on ectopic lenses has previously been controversial, due to the risk of sightthreatening complications. In paper I we studied retrospectively visual outcomes and complications in children, who were operated for congenital EL, and who had en scleral-fixated capsular tension ring (CTR) and an intra-ocular lens (IOL) implanted at the primary surgery. Thirty-seven eyes of 22 children were included. Visual acuity (VA) improved in all eyes, and only few had persistent amblyopia at the end of the follow-up. A great majority of the eyes had postoperative visual axis opacification (VAO), which was expected, since the posterior capsule was left intact at the primary surgery. Two eyes required secondary suturing for IOL decentration. No eye had any serious complications such as retinal detachment, glaucoma or endophthalmitis. Congenital ectopia lentis is often an indicator of a systemic connective tissue disorder, and Marfan syndrome (MFS) is diagnosed in 70% of the cases. This genetic disorder affects basically all organ systems in the body, EL and dilatation of the ascending aorta being the cardinal signs. MFS is associated with markedly decreased life expectancy due to the cardiovascular complications. Therefore, an early and accurate diagnosis is of importance. In paper II we measured the accommodative power, lens thickness, anterior chamber depth (ACD), and pupil size in these eyes, using an optical coherence tomography (OCT). Thirty-one eyes of 31 cases of MFS were included, and these were compared to non-affected controls. We found that the lens was significantly thicker in MFS at all stages. The pupil size was significantly smaller in MFS at baseline, decreased less in accommodation and dilated more during dilatation. No significant difference was seen in the accommodative power or ACD. No difference was seen in any parameter between the MFS eyes with, and without EL. We conclude, that even though the lens and the pupil seem to be affected in MFS, these eyes seem to have the same ability to accommodate as normal subjects. The observed changes seem to be associated to MFS independently of EL. In paper III we studied the corneal curvature, thickness and endothelial cell density (ECD) in 39 MFS eyes and compared those to non-affected controls. We found significantly lower keratometric (K) values and corneal thickness in MFS, but no difference in the ECD. No significant difference was found in these parameters between MFS eyes with and without EL. We also reported on generally increased corneal astigmatism in MFS, especially in eyes with EL. In paper IV we described the ocular characteristics in 102 eyes of 56 cases of MFS. We found increased axial length, but mostly only moderate myopia, which seemed to be compensated by the flat cornea. The majority of the eyes had EL, or were pseudophakic due to EL. Other associated diagnosis included amblyopia, glaucoma, retinal detachment and strabismus. In conclusion, we found that surgery for EL in children, including CTR and IOL gives good visual development and no serious complications. Also, most of the ocular changes in MFS seem to be connected to MFS itself, rather than EL

Multiple uses of water in irrigated areas: a case study from Sri Lanka

Water management / Water allocation / Water use efficiency / Irrigated farming / Water resources development / Water policy / Water quality / Domestic water / Water users' associations / Water rights / Gender / Households / Pricing / Water costs / Case studies / Sri Lanka / Kirindi Oya

Safe storage of pesticides in Sri Lanka – Identifying important design features influencing community acceptance and use of safe storage devices

<p>Abstract</p> <p>Background</p> <p>Self-poisoning with pesticides is the cause of an estimated 300,000 deaths annually in rural Asia. The great majority of these deaths are from impulsive acts of self-harm using pesticides that are readily available in the home. The secure storage of pesticides under lock has been emphasized as a possible answer to the problem. This aspect, however, has been poorly researched. In this paper, we report on the design and use, in rural Sri Lanka, of a variety of different lockable storage devices.</p> <p>Methods</p> <p>Following a baseline survey of pesticide storage practices, randomly selected households received a pesticide safe storage device. The study was conducted in two phases. In the first phase a total of 200 households in two villages were provided with in-house safe storage devices and two follow-up surveys were conducted seven and 24 months after distribution. The results of the seven month post-distribution survey have already been published. In the second phase, a further 168 households were selected in two additional villages and given a choice between an in-house and an in-field storage device and a follow-up survey conducted seven months after distribution. Both follow-up surveys aimed to assess the use of the device, obtain detailed user feedback on the different storage designs, and to identify problems faced with safeguarding the key. Twelve focus group discussions were held with representatives of households that received a storage device to derive from the community qualitative feedback on the design requirements for such devices.</p> <p>Results</p> <p>One hundred and sixty one of the 200 households selected during the first phase were using pesticides at the time of the follow-up survey, 24 months after distribution. Of these 161 households 89 (55%) had the pesticides stored and locked in the provided device. Among the 168 households that were given a choice between an in-house and an in-field storage device 156 used pesticides at the time of survey and of these 103 (66%) selected in-field storage devices and 34% chose in-house storage devices. Of the 156 households, 106 (68%) stored all pesticides in a locked storage device at the time of the follow-up survey seven months after distribution. The majority of households that received an in-field storage device chose to install the device within their compound rather than in the field as they were concerned about the possibility of theft. The preferred design of the storage device was influenced by a number of occupational factors such as land size, crop patterns, types and the quantity of pesticides used. The presence of termites, perceived safety, material used to manufacture the device and ease of location influenced their choice. The study revealed that it was difficult to keep the key to the device hidden from children; and that the person in charge of the key would have easy access to the stored poison.</p> <p>Conclusion</p> <p>This study confirms the high acceptance of lockable storage devices by the community although the use of the device reduced over time. A large proportion of pesticides stored within the compound after the introduction of the device may have implications for accessibility to pesticides in the domestic environment. The ability of other household members, including children, to easily find the key is also worrying.</p

Malaria in Sri Lanka: Current knowledge on transmission and control

Malaria / Disease vectors / Waterborne diseases / Environmental effects / Public health / Economic impact / Social impact / Sri Lanka